engleski

Lifelong changes after perinatal moderate hypoxia: increased number of interneurons and perineuronal nets in the cingulate cortex of the adult rat

We designed a non-invasive model in newborn rats to determine the hallmarks of possible permanent structural and behavioral changes in the brain after moderate perinatal hypoxia. The 82 Wistar Han (RccHan: WIST) rats were randomly subjected to hypoxia (pO2 73mmHg/2h) or normoxia at the first postnatal day. The increase of hypoxia-inducible factor-1α and decreased cytochrome-C-oxygenase expression in treated animals' brains, detected by Western blot, confirmed an acute moderate lesion. The results of the open-field, hole-board, social- choice, and T-maze tests, applied at the 30 - 45th and 70-85th postnatal days, displayed significant hyperactivity and a slower pace of learning in rats subjected to perinatal hypoxia. At 3.5 months of age, the histochemical examination revealed a significantly increased number of specific extracellular matrix-perineuronal nets and parvalbumin-expressing interneurons in the medial and retrosplenial cingulate cortex of these animals. Conclusively, moderate perinatal hypoxia in the rat causes lifelong cellular and connectivity organization changes in the cingulate cortex and related behavioral and cognitive alterations. This non-invasive hypoxia in the rat successfully and complementary models the frequently unrecognized moderate perinatal brain injury in fetuses in humans and may enhance future research of new diagnostic and therapeutic strategies for perinatal brain injuries.

learning pattern ; connectivity development ; oxidative stress ; hyperactivity behavior

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